Working Paper Article Version 1 This version is not peer-reviewed

Decreased Excitatory Drive onto Hilar Neuronal Nitric Oxide Synthase Expressing Interneurons in Chronic Model of Epilepsy

Version 1 : Received: 24 November 2020 / Approved: 25 November 2020 / Online: 25 November 2020 (10:19:05 CET)

How to cite: Wang, X.; Zhang, Y.; Cheng, W.; Gao, Y.; Li, S. Decreased Excitatory Drive onto Hilar Neuronal Nitric Oxide Synthase Expressing Interneurons in Chronic Model of Epilepsy. Preprints 2020, 2020110630 Wang, X.; Zhang, Y.; Cheng, W.; Gao, Y.; Li, S. Decreased Excitatory Drive onto Hilar Neuronal Nitric Oxide Synthase Expressing Interneurons in Chronic Model of Epilepsy. Preprints 2020, 2020110630

Abstract

Excitation-inhibition imbalance of GABAergic interneurons is predisposed to develop chronic temporal lobe epilepsy (TLE). We have previously shown that virtually every neuronal nitric oxide synthase (nNOS)-positive cell is a GABAergic inhibitory interneuron in the denate gyrus. The present study was designed to quantify the number of nNOS-containing hilar interneurons using stereology in pilocapine- and kainic acid (KA)-exposed transgenic adult mice that expressed GFP under the nNOS promoter. In addition, we studied the properties of miniature excitatory postsynaptic current (mEPSC) and paired-pulse response ratio (PPR) of evoked EPSC in nNOS interneurons using whole cell recording techniques. Results showed that there were fewer nNOS-immunoreactive interneurons of chronically epileptic animals. Importantly, patch-clamp recordings revealed reduction in mEPSC frequency, indicating diminished global excitatory input. In contrast, PPR of evoked EPSC following the granule cell layer stimulation was increased in epileptic animals suggesting reduced neurotransmitter release from granule cell input. In summary, we propose that impaired excitatory drive onto hippocampal nNOS interneurons may be implicated in the development of refractory epilepsy.

Keywords

nNOS; Temporal lobe epilepsy; Interneuron; Synaptic transmission; Mouse models

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